The overall objective of the proposed research is to define the roles of cholesterol "esterases" in cholesterol absorption and to selectively inhibit the enzyme(s) as a means of preventing cholesterol absorption. The specific objectives include: 1. To prepare specific antibodies to pancreatic cholesterol esterase and employ these antibodies to determine the partial identity of the low energy cholesterol esterase of intestine and aorta and the intracellular localization of mucosal cholesterol esterase by antigen-tagged antibody reaction. 2. To determine if pancreatic cholesterol esterase is the essential factor in pancreatic juice required for cholesterol absorption and if pancreatic cholesterol esterase is the source of the "mucosal" enzyme. 3. To evaluate the effectiveness of chemical inhibitors of cholesterol esterase as a means of controlling cholesterol absorption. The inhibitors will be screened using the isolated absorptive cell model. Effective in vitro inhibitors will be tested for their effectiveness in preventing cholesterol absorption in lymph-duct cannula animals. 4. To determine the role of chylomicrons and VLDLs in cholesterol transport. The isolated absorptive cell model which packages and releases lipoproteins will be employed. 5. To determine in a collaboraive effort the metabolic defect in the genetic abnormality, beta-sitosterolemia. Details of sitosterol absorption will be studied in absorptive cells isolated from sitosterolemia patients.